Zhenwu Decoction Attenuates Water‐Retention–Related Phenotypes and Multiorgan Injury in Rats With Doxorubicin‐Induced Chronic Heart Failure

OBJECTIVE: This study is aimed at evaluating the effects of Zhenwu Decoction (ZWD) on cardiac dysfunction, water-retention-related phenotypes, and brain and kidney injury in rats with doxorubicin-induced chronic heart failure (CHF), and at examining whether these effects were accompanied by changes in AVP, V2R, PKA-Cα, and AQP2-related markers. METHODS: Rats that met the prespecified CHF criteria after doxorubicin administration were rerandomized to the model, ZWD-L, ZWD-M, ZWD-H, or tolvaptan groups and treated once daily for 14 consecutive days. Cardiac function, biochemical and water balance-related outcomes, histopathology, brain AVP, and renal V2R, PKA-Cα, and AQP2 expression were assessed. The animal was the experimental unit, and the number analyzed is reported for each outcome. RESULTS: Compared with the control group, model rats showed impaired cardiac function; increased ascites and tissue water retention; reduced 24-h urine output; histological injury in the heart, brain, and kidney; and altered AVP, V2R, PKA-Cα, and AQP2-related markers. ZWD treatment was associated with improvement in these measured outcomes, with the magnitude and statistical support varying across doses. Tolvaptan produced the expected aquaretic reference response. Adjusted p values and the number of animals analyzed are reported for each outcome. CONCLUSION: In this doxorubicin-induced CHF model, ZWD improved cardiac function and water-retention-related phenotypes and was accompanied by changes in AVP, V2R, PKA-Cα, and AQP2-related markers. These data support an association but do not establish pathway mediation, direct target engagement, or heart-brain-kidney crosstalk.